Different Expression Patterns of Toll-Like Receptor mRNAs in Blood Mononuclear Cells of IgA Nephropathy and IgA Vasculitis with Nephritis

Different Expression Patterns of Toll-Like Receptor mRNAs in Blood Mononuclear Cells of IgA Nephropathy and IgA Vasculitis with Nephritis

AYANO SAITO,¹ ATSUSHI KOMATSUDA,¹ HAJIME KAGA,¹ RYUTA SATO,¹ MASARU TOGASHI,¹ SHIN OKUYAMA,² HIDEKI WAKUI^1,3 and NAOTO TAKAHASHI¹

¹Department of Hematology, Nephrology and Rheumatology, Akita University Graduate School of Medicine, Akita, Akita, Japan
²Center for Kidney Disease and Transplantation, Akita University Hospital, Akita, Akita, Japan
³Department of Life Science, Akita University Graduate School of Engineering Science, Akita, Akita, Japan

Mucosal immunity may play a key role in IgA nephropathy (IgAN) and IgA vasculitis with nephritis (IgAVN). IgAVN is characterized by the presence of non-thrombocytopenic palpable purpura, associated with glomerulonephritis with IgA-dominant immune deposits. Recent studies have shown the up-regulation of Toll-like receptors (TLRs) in patients with IgAN or IgAVN. Among TLRs that mediate innate immune reactions, TLR2, TLR4, and TRL5 recognize bacterial components, while TLR3, TLR7, and TLR9 recognize viral components. Here we compared the expression levels of TLR mRNAs in peripheral blood mononuclear cells (PBMCs) from 49 IgAN patients, 20 IgAVN patients, and 20 patients with thin basement membrane nephropathy (TBMN), unrelated to immune-mediated pathogenesis, as a control. The real-time RT-PCR analysis revealed the significantly higher expression levels of TLR2, TLR3, TLR5, TLR7, and TLR9 mRNAs in PBMCs of IgAN and IgAVN patients, compared to TBMN patients. Importantly, TLR4 mRNA levels were significantly higher in IgAN patients than in IgAVN patients, while its expression levels were comparable in IgAVN patients and TBMN patients. In contrast, TLR5 and TLR9 mRNA levels were significantly higher in IgAVN patients than in IgAN patients. In IgAN patients, expression levels of TLR2, TLR3, TLR5, or TLR9 mRNA were correlated with proteinuria levels, and TLR4 mRNA levels were correlated with serum IgA levels. In IgAVN patients, however, there was no such correlation. The up-regulated expression of TLR mRNAs in PBMCs may be related to the development of IgAN and IgAVN. The distinct expression patterns between these two diseases may reflect their different pathogenetic mechanisms.

keywords —— Keywords: IgA nephropathy; IgA vasculitis; peripheral blood mononuclear cells; real-time reverse transcription polymerase chain reaction; Toll-like receptors

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Tohoku J. Exp. Med., 2016, 240, 199-208

Correspondenc: Atsushi Komatsuda, Department of Hematology, Nephrology and Rheumatology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, Akita 010-8543, Japan.

e-mail: komatsud@med.akita-u.ac.jp